This Career Development Award will support the growth of Dr. Daniel Licht into an independent clinical investigator with specialization in pediatric cerebrovascular injury. Dr. Licht's primary career development goal is to establish a multi-disciplinary research program encompassing the fields of neurology, critical care, and neuroimaging. To achieve these goals, Dr. Licht proposes collaborations between physicists and clinicians to develop new non-invasive methods for measuring cerebral blood flow (CBF) in newborn infants. Through modification and application of new imaging technologies, the proposed research will investigate the role of CBF in acquired brain injury in infants with severe congenital heart defects (CHD). CBF represents an important physiologic parameter for the understanding, diagnosis and management of neonatal brain disorders, and plays a pivotal role in brain injury in infants with severe CHD before heart surgery. In previous studies, Dr. Licht has found that deranged cerebrovascular physiology was associated with pre-operative structural brain injury. To further investigate this association, he proposes to measure and compare global and regional brain volumes in infants with CHD to those without CHD, and determine whether these differences are related to an altered CBF. Dr. Licht will use MRI based techniques to make these measurements and will test diffuse optic tomography (DOT) for comparative measurements. To date, both normative and disease data on pediatric brain perfusion remain sparse due to the lack of suitable techniques for CBF measurement. DOT is complimentary to MRI in that it offers excellent temporal resolution and can be applied at the point of care. Furthermore, DOT offers concurrent analysis of metabolic rate while sacrificing only mild anatomic resolution. [unreadable] [unreadable]